Tryrotropin releasing hormone (TRH) is a tripeptide which in addition to its ability to stimulate certain cells in the pituitary gland, has profound effects on animal behavior. Some of the responses which are altered by TRH are also altered by changes in serotonin availability or receptor stimulation. We wish to explore the degree to which the extrahypothalamic TRH containing neurons and serotonin neurones are related to each other, both anatomically and functionally. Initially, we wish to expand our preliminary observation that a compound which destroys serotonin neurones also reduces TRH in brain. This will be followed by an attempt to see if the localization of TRH immunoreactive neurones are related to serotonergic neurones, and if exogenous TRH in turn alters serotonin availability. Using 2-deoxyglucose, the regional specificity of TRH-induced metabolic activation will be assessed with both histochemical and quantitative biochemical techniques. This data will be correlated with TRH receptor distribution in different regions of brain, both in adults and developing rats. The anxiolytic and respiratory stimulant effects of exogenous TRH will be examined in rats with deficient serotonergic neuronal populations, in order to detect interaction of these two endogenous neuronal systems. Since thyroid deficiency and CNS serotonergic mechanisms can both alter the threshold of rats to develop audiogenic seizures, the involvement of both TRH and serotonin neuronal systems in audiogenic seizures will be quantitated. Finally, we will pursue the initial steps required to be able to measure synthesis and utilization of TRH in the CNS. It is hoped that these studies will provide a background for understanding the interrelationships of TRH and serotonin, and thus permit the development of a better understanding of a variety of abnormal CNS functions. Although the cause of neonatal hypothyroidism is still unknown, animal studies suggest that intervention in serotonin mechanisms can alter thyroid status75. Perhaps our findings will offer a more complete understanding of the pathogenesis and thus prevention of neonatal hypothyroidism.